An estimated 30% of chronic stroke patients with motor disabilities of the limbs are plegic in the hand or the foot - that is, they cannot move the hand or foot. While some plegic stroke patients have completely paralyzed muscles, without the ability to activate even minimally the plegic muscles ("profound plegia"), other plegic stroke patients are capable of producing volitional muscle activation, but are not strong enough to make the joint move ("pseudo plegia"). The long-term objective of this study is to restore functional movement to stroke patients with profoundly plegic muscles and with pseudo plegic muscles. Stroke is the leading cause of disability in the U.S., amounting to $50 billion in health care costs annually. Each year, about 700,000 US citizens suffer stroke, and those who survive without full recovery join a growing population of chronically disabled individuals currently totaling 5.8 million. Any therapeutic intervention that effectively treats plegic stroke patients will have significant impact on the productivity, quality of life, and healthcare expenses of stroke patients in the U.S. and worldwide. The work proposed in this application addresses the treatment of low functioning plegic stroke patients through the use of a recently developed therapeutic intervention called "AMES" (Assisted Movement with Enhanced Sensation). AMES therapy involves a robotic device that moves the paretic or plegic joint while the patient assists the motion and observes visual biofeedback - in the form of joint torque for paretic individuals, or muscle activity (EMG) for plegic individuals - about their level of assistance. While the robotic device moves the joint, vibrators on the AMES therapy device stimulate sensory receptors in the lengthening muscles to enhance the sensation of joint motion and displacement. AMES treatment has already been shown to be an effective treatment for most low-functioning stroke patients with paresis, helping them regain functional movement. In Aim 1, we will redesign the robotic grasp mechanism of the AMES device to increase its sensitivity so that it will be able to measure low levels of torque during AMES hand therapy - at levels beyond the capacity of the current AMES device. This increased sensitivity will allow us to detect with precision the point at which AMES therapy causes a patient to transition from plegia to paresis. In Aim 2, using AMES therapy combined with brain stimulation (rTMS or tDCS), our goal is to restore volitional EMG to profoundly plegic muscles and, thereby, convert these muscles into pseudo plegic muscles. PUBLIC HEALTH RELEVANCE: The proposed research addresses the sensorimotor rehabilitation of low-functioning stroke patients with hand plegia, a sub-population not served by currently available therapeutic approaches. The objective is to use "AMES" therapy in combination with brain stimulation to restore volitional muscle activity in this population. AMES+brain stimulation is envisioned to be the first of 3 forms of AMES therapy in a progressive therapeutic regimen for profoundly plegic stroke patients that would, first, restore volitional muscle activity (EMG) via AMES+brain stimulation, next, restore some minimal movement via AMES+EMG biofeedback, and lastly, restore functional movement via AMES+torque biofeedback.